The ethics of research involving animals - Nuffield Council on ...
The ethics of research involving animals - Nuffield Council on ...
The ethics of research involving animals - Nuffield Council on ...
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T h e e t h i c s o f r e s e a r c h i n v o l v i n g a n i m a l s<br />
For complete replacement <str<strong>on</strong>g>of</str<strong>on</strong>g> <str<strong>on</strong>g>animals</str<strong>on</strong>g>, an alternative method should not require any<br />
animal-derived biological material. Examples <str<strong>on</strong>g>of</str<strong>on</strong>g> such methods or approaches include the<br />
use <str<strong>on</strong>g>of</str<strong>on</strong>g> predicti<strong>on</strong>s based <strong>on</strong> the physical and chemical properties <str<strong>on</strong>g>of</str<strong>on</strong>g> molecules,<br />
mathematical and computer studies <str<strong>on</strong>g>of</str<strong>on</strong>g> biological processes, analysis <str<strong>on</strong>g>of</str<strong>on</strong>g> epidemiological<br />
data, <str<strong>on</strong>g>research</str<strong>on</strong>g> <str<strong>on</strong>g>involving</str<strong>on</strong>g> human participants or <str<strong>on</strong>g>research</str<strong>on</strong>g> <strong>on</strong> isolated human cells and<br />
tissues in culture (see Box 11.1). However, many methods c<strong>on</strong>sidered as Replacements also<br />
use some biological material obtained from living or humanely killed <str<strong>on</strong>g>animals</str<strong>on</strong>g>. <str<strong>on</strong>g>The</str<strong>on</strong>g>se<br />
include <str<strong>on</strong>g>research</str<strong>on</strong>g> <strong>on</strong> cells and tissues derived from living or humanely killed <str<strong>on</strong>g>animals</str<strong>on</strong>g> for<br />
culture in vitro and animal-derived growth supplements such as serum derived from fetal<br />
or newborn calves. <str<strong>on</strong>g>The</str<strong>on</strong>g>se methods can be called incomplete Replacements. 4<br />
Box 11.1: Complete and incomplete<br />
replacements<br />
Computer studies and in vitro methods<br />
Mathematical and computer modelling studies (in<br />
silico techniques) comprise a variety <str<strong>on</strong>g>of</str<strong>on</strong>g> approaches.<br />
<str<strong>on</strong>g>The</str<strong>on</strong>g>y include the predicti<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> the biological activity <str<strong>on</strong>g>of</str<strong>on</strong>g><br />
substances, and the modelling <str<strong>on</strong>g>of</str<strong>on</strong>g> biochemical,<br />
physiological, pharmacological, toxicological and<br />
behavioural systems and processes.* In vitro<br />
techniques are also varied, increasing in complexity<br />
from subcellular (cell-free) fracti<strong>on</strong>s, through primary<br />
cells and cell lines grown in liquid suspensi<strong>on</strong>, and<br />
three-dimensi<strong>on</strong>al cultures, to tissue slices or<br />
fragments and even whole perfused organs, all<br />
c<strong>on</strong>sisting <str<strong>on</strong>g>of</str<strong>on</strong>g> cells or tissues derived from <str<strong>on</strong>g>animals</str<strong>on</strong>g> or<br />
humans.† Examples <str<strong>on</strong>g>of</str<strong>on</strong>g> techniques that involve cells,<br />
tissues or organs from <str<strong>on</strong>g>animals</str<strong>on</strong>g> that have been killed<br />
humanely include: the use <str<strong>on</strong>g>of</str<strong>on</strong>g> guinea pig skin to<br />
provide informati<strong>on</strong> that would previously have been<br />
obtained from tests <strong>on</strong> the skin <str<strong>on</strong>g>of</str<strong>on</strong>g> living <str<strong>on</strong>g>animals</str<strong>on</strong>g>, or<br />
the use <str<strong>on</strong>g>of</str<strong>on</strong>g> primary cell cultures to replace ne<strong>on</strong>atal<br />
mice as a virus isolati<strong>on</strong> or assay system.<br />
Human studies<br />
In many types <str<strong>on</strong>g>of</str<strong>on</strong>g> biomedical and toxicological<br />
<str<strong>on</strong>g>research</str<strong>on</strong>g>, <str<strong>on</strong>g>animals</str<strong>on</strong>g> are used because ethical<br />
c<strong>on</strong>siderati<strong>on</strong>s preclude c<strong>on</strong>ducting the experiments<br />
<strong>on</strong> humans. However, a number <str<strong>on</strong>g>of</str<strong>on</strong>g> approaches have<br />
been suggested which, in some cases, might replace<br />
the use <str<strong>on</strong>g>of</str<strong>on</strong>g> <str<strong>on</strong>g>animals</str<strong>on</strong>g> with studies <strong>on</strong> humans. <str<strong>on</strong>g>The</str<strong>on</strong>g>se<br />
include n<strong>on</strong>-invasive brain scanning to replace some<br />
experiments <strong>on</strong> primates,‡ and studies <strong>on</strong> ultra-lowdose<br />
ADME metabolism in human volunteers in the<br />
early stages <str<strong>on</strong>g>of</str<strong>on</strong>g> selecti<strong>on</strong> for potential medicines.∫<br />
Human tissue samples can be used both for direct<br />
examinati<strong>on</strong> (e.g. histopathology) and in cell culture<br />
and other in vitro techniques.**<br />
* Using, for example, molecular modelling and the<br />
development <str<strong>on</strong>g>of</str<strong>on</strong>g> quantitative structure-activity<br />
relati<strong>on</strong>ships; see Combes RD and Juds<strong>on</strong> P (1995) <str<strong>on</strong>g>The</str<strong>on</strong>g><br />
use <str<strong>on</strong>g>of</str<strong>on</strong>g> artificial intelligence systems for predicting<br />
toxicity Pest Sci 45:179–94; Combes RD and Rodford R<br />
(2003) <str<strong>on</strong>g>The</str<strong>on</strong>g> use <str<strong>on</strong>g>of</str<strong>on</strong>g> expert systems for toxicity predicti<strong>on</strong> –<br />
illustrated with reference to the DEREK program, in<br />
Modelling Envir<strong>on</strong>mental Fate and Toxicity Cr<strong>on</strong>in M and<br />
Livingst<strong>on</strong>e D (Editors) (L<strong>on</strong>d<strong>on</strong>: Taylor & Francis);<br />
Assessing the cumulative effect <str<strong>on</strong>g>of</str<strong>on</strong>g> mutati<strong>on</strong>s: Kirkwood<br />
TB & Proctor CJ (2003) Somatic mutati<strong>on</strong>s and ageing in<br />
silico Mech Ageing Dev 124:85–92.<br />
† <str<strong>on</strong>g>The</str<strong>on</strong>g> European Collecti<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> Cell Cultures (ECACC)<br />
operates a cell bank <str<strong>on</strong>g>of</str<strong>on</strong>g> peripheral lymphocytes from<br />
approximately 40,000 d<strong>on</strong>ors. Forty percent are in the<br />
form <str<strong>on</strong>g>of</str<strong>on</strong>g> lymphoblastoid cell lines representing around<br />
450 genetic disorders. <str<strong>on</strong>g>The</str<strong>on</strong>g>se lines are useful for the<br />
analysis <str<strong>on</strong>g>of</str<strong>on</strong>g> the role <str<strong>on</strong>g>of</str<strong>on</strong>g> genes in disorders that have a<br />
genetic comp<strong>on</strong>ent, for example cardiovascular diseases,<br />
Alzheimer’s disease or depressi<strong>on</strong>.<br />
‡ Langley G, Harding G, Hawkins P, et al. (2000) Volunteer<br />
studies replacing animal experiments in brain <str<strong>on</strong>g>research</str<strong>on</strong>g><br />
Alternat Lab Anim 28: 315–31.<br />
∫<br />
In this type <str<strong>on</strong>g>of</str<strong>on</strong>g> <str<strong>on</strong>g>research</str<strong>on</strong>g>, the absorpti<strong>on</strong>, distributi<strong>on</strong>,<br />
metabolisati<strong>on</strong> and excreti<strong>on</strong> (ADME) <str<strong>on</strong>g>of</str<strong>on</strong>g> new medicines is<br />
assessed by measuring the effects <str<strong>on</strong>g>of</str<strong>on</strong>g> administering<br />
extremely low doses <str<strong>on</strong>g>of</str<strong>on</strong>g> candidate compounds.<br />
Extrapolati<strong>on</strong>s are then made c<strong>on</strong>cerning the effects <str<strong>on</strong>g>of</str<strong>on</strong>g><br />
higher doses. <str<strong>on</strong>g>The</str<strong>on</strong>g> approach is at the early stages <str<strong>on</strong>g>of</str<strong>on</strong>g><br />
development and is not yet suited to replace the use <str<strong>on</strong>g>of</str<strong>on</strong>g><br />
<str<strong>on</strong>g>animals</str<strong>on</strong>g> in pharmaceutical <str<strong>on</strong>g>research</str<strong>on</strong>g>. Combes RD, Berridge<br />
T, C<strong>on</strong>nelly J et al. (2003) Early microdose drug studies in<br />
human volunteers can minimise animal testing.<br />
Proceedings <str<strong>on</strong>g>of</str<strong>on</strong>g> a workshop organised by volunteers in<br />
<str<strong>on</strong>g>research</str<strong>on</strong>g> and testing Eur J Pharm Sci 19: 1–11.<br />
** Access to patients and issues <str<strong>on</strong>g>of</str<strong>on</strong>g> c<strong>on</strong>sent are critical factors<br />
in the feasibility <str<strong>on</strong>g>of</str<strong>on</strong>g> human studies, see paragraph 11.26.<br />
CHAPTER 11 REPLACEMENTS<br />
11.7 Tests using invertebrates, or early developmental stages <str<strong>on</strong>g>of</str<strong>on</strong>g> vertebrates (i.e. before they<br />
reach the point at which their use in experiments and other scientific procedures is<br />
regulated), are also sometimes described as Replacements, even though they do not<br />
replace <str<strong>on</strong>g>animals</str<strong>on</strong>g> per se. For example, the horseshoe crab (Limulus) can be used to replace<br />
4 Although this practice does not replace the use <str<strong>on</strong>g>of</str<strong>on</strong>g> <str<strong>on</strong>g>animals</str<strong>on</strong>g> per se, it replaces the carrying out <str<strong>on</strong>g>of</str<strong>on</strong>g> procedures <strong>on</strong> living <str<strong>on</strong>g>animals</str<strong>on</strong>g>.<br />
Sacrificing the life <str<strong>on</strong>g>of</str<strong>on</strong>g> <strong>on</strong>e animal can save the lives <str<strong>on</strong>g>of</str<strong>on</strong>g> many other <str<strong>on</strong>g>animals</str<strong>on</strong>g>, as its organs and tissues can be used in many<br />
different experiments. <str<strong>on</strong>g>The</str<strong>on</strong>g> humane killing <str<strong>on</strong>g>of</str<strong>on</strong>g> an animal carried out according to methods prescribed in Schedule 1 <str<strong>on</strong>g>of</str<strong>on</strong>g> the A(SP)A<br />
is not counted as a procedure.<br />
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